HCAR1-Mediated L-Lactate Signaling Suppresses Microglial Phagocytosis

Abstract

Microglia, the primary brain-resident immune cells, protect the brain from various harmful pathogens, insulting and maintaining its homeostasis by phagocytosing extracellular particles. How microglia are metabolically regulated by their microenvironment remains largely elusive. Here, we investigated how extracellular lactate, which is abundant in the brain and dynamically changes in pathological states, affects microglial phagocytotic ability. We show that L-lactate reduces microglia phagocytic capacity in a Hydroxycarboxylic Acid Receptor 1 but not Monocarboxylate transporter 1-dependent manner. Our findings point to a potential role for extracellular lactate in suppressing the phagocytic activity of microglial cells in homeostasis and inflammatory conditions.

Keywords: Amyloid-beta; HCAR1; Lactate; Microglia; Phagocytosis.